Bi-layered hydrogel conduit integrating microneedles for enhanced neural recording and stimulation therapy in peripheral nerve injury repair

Nerve conduit is an alternative strategy in peripheral nerve injuries (PNI) treatment both for neural signals recording and therapeutic electrical stimulation (ES). Most conventional conduits suffer from surgical suturing and lacking real-time insights of nerve recovery, as well as failing in integrating therapy strategies. Herein, we introduce a bi-layered hydrogel conduit with microneedles (BHCM), in which poly (N-isopropylacrylamide) (PNIPAm)-incorporated polyethyleneimine (PEI) forms the outer layer for conductivity and electro-driven drug loading and release, whereas PNIPAm/alginate/tannic acid hydrogel (PNIPAm/SA/TA) forms the inner layer to ensure biocompatible mechanics and strong tissue adhesion. Meanwhile, the differences in doping manipulated different critical solution temperature (LCST) and swelling between the double layers determine the self-curling performance. Therefore, the BHCM responds to temperature and self-curls into conduit to wrap and bind to sciatic nerve, avoiding the complicated suturing and enhancing the interfacial electrical transmission. By puncturing the epineurium, the microneedles strongly enhance the electrochemical performance, and synergistically facilitate controllable drug delivery as well as electrical stimulation and recording efficiency. Further, BHCM is demonstrated to regulate macrophage polarization from M1 to M2 through electrically stimulated Rhein release, thereby reducing inflammation and facilitating diabetic PNI repair. The present design aims to improve biosafety, surgical simplicity to realize overall recovery of injured nerves, making it a promising candidate for advanced peripheral nerve repair strategies.